Project Summary: Pancreatic cancer (PaC) is a devastating and poorly understood cancer. In the year 2005, an estimated 32,180 new cases of pancreatic adenocarcinoma are projected to be diagnosed, of which 31,800 are expected to die from this disease. Symptoms of pancreatic carcinoma including weight loss, anorexia, epigastric discomfort, and back pain are non-specific and vague, so diagnosis may be considerably delayed. Consequently fewer than 20% of patients have resectable disease by the time the diagnosis is made. Thus, among the most compelling needs for PaC today is to develop a rational, evidence-based strategy to screen for early PaC. The purpose of the proposed studies is to identify novel biomarkers that will aid in the diagnosis of early pancreatic cancer. Towards this goal we have assembled a strong investigative team that includes basic scientists with extensive experience in proteomics and biostatistical expertise combined with the clinical skills of surgical oncologists with a particular interest in early detection and treatment of pancreatic cancer. A state-of-the-art two-dimensional liquid chromatography system will be used to prepare serum protein profiles from patients with resectable PaC and control subjects that include patients with benign pancreatic disease, other gastrointestinal malignancies, and healthy individuals. Classification models comprised of a panel of biomarkers that can correctly classify PaC patient serum from controls will be derived from the protein profiles and verified using an independent set of serum protein profiles. The individual proteins composing the panel of biomarkers will then be identified by tandem mass spectrometry. Changes in the serum level of these potential diagnostic biomarkers will also be monitored in serum collected postoperatively from patients who have undergone pancreatic resection for PaC. Using cutting-edge proteomic technologies, we anticipate the identification of a panel of biomarkers that may be used for early detection of this devastating disease; thus allowing us to rapidly advance the translation of our basic science findings into the clinic. Relevance: Currently, there are no reliable screening tests available for early diagnosis of pancreatic cancer. As surgical resection is the only curative intervention for pancreatic cancer, there is a desperate need for better methods of detection of this disease at an early, operable stage. In this study, we will use state-of-the- art technologies to identify proteins in serum that may be used for early detection of pancreatic cancer and thus have a profound impact upon the diagnosis and treatment of patients with this disease. [unreadable] [unreadable] [unreadable]